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Spinal cord injury induced neuropathic pain: Molecular targets and therapeutic approaches

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Abstract

Neuropathic pain, especially that resulting from spinal cord injury, is a tremendous clinical challenge. A myriad of biological changes have been implicated in producing these pain states including cellular interactions, extracellular proteins, ion channel expression, and epigenetic influences. Physiological consequences of these changes are varied and include functional deficits and pain responses. Developing therapies that effectively address the cause of these symptoms require a deeper knowledge of alterations in the molecular pathways. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are two promising therapeutic targets. Matrix metalloproteinases interact with and influence many of the studied pain pathways. Gene expression of ion channels and inflammatory mediators clearly contributes to neuropathic pain. Localized and time dependent targeting of these proteins could alleviate and even prevent neuropathic pain from developing. Current therapeutic options for neuropathic pain are limited primarily to analgesics targeting the opioid pathway. Therapies directed at molecular targets are highly desirable and in early stages of development. These include transplantation of exogenously engineered cell populations and targeted gene manipulation. This review describes specific molecular targets amenable to therapeutic intervention using currently available delivery systems.

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Acknowledgments

The authors are thankful to Dr. Jay Yang, Professor, Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI for initial guidance to write this review. Scholarly assistance from Hung Tae Kim, Carrie Nacht, and Steven Siegel is duly acknowledged. All work was funded through the UW Madison Department of Neurological Surgery. The authors declare that they have no conflicts of interest. The manuscript does not contain clinical studies of patient data.

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  1. Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792, USA

    Dominic Schomberg, Gurwattan Miranpuri, Andrew Crowell, Raghu Vemuganti & Daniel Resnick

  2. Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, 1300 University Ave, Madison, WI, 53706, USA

    Tyler Duellman

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Schomberg, D., Miranpuri, G., Duellman, T. et al. Spinal cord injury induced neuropathic pain: Molecular targets and therapeutic approaches. Metab Brain Dis 30, 645–658 (2015). https://doi.org/10.1007/s11011-014-9642-0

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  • DOI: https://doi.org/10.1007/s11011-014-9642-0

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